West Coast Editor

Guilford Pharmaceuticals Inc. on Thursday said adjustments in its voluntarily suspended Phase III study with Aquavan may extend only "modestly" the time to filing a new drug application, but Wall Street proved unforgiving, as investors took away more than 33 percent of the stock's value.

The company's shares (NASDAQ:GLFD) fell $1.19 that day, to close at $2.34. Nasdaq was closed Friday for the holiday.

Given Aquavan's high-profile status for Baltimore-based Guilford, "combined with a number of high-profile disappointments of late, there's a high degree of sensitivity in the market currently," noted Stacey Jurchison, director of corporate communications for the company.

Aquavan found itself caught "right in those crosshairs," she said.

Possibly mitigating the damage was good news from the study: Aquavan met its primary efficacy endpoint with no serious adverse events. Investigators compared the compound, a water-soluble prodrug of propofol, with midazolam for sedation of patients undergoing colonoscopy.

The primary efficacy endpoint was success of sedation, defined as three consecutive Modified Observer's Assessment of Alertness/Sedation scores less than or equal to four, and completing the procedure without employing alternative sedative medications or ventilation.

Aquavan resulted in a 96 percent sedation success, with deeper levels of sedation for longer periods compared to patients who received midazolam - which led to a higher level of adverse events in the Aquavan patients, who showed a median time to sedation of two minutes and a median time to full recovery from the end of the procedure of 11 minutes.

Quick onset and quick recovery are the sought-after features of such a drug, so a lower dose of Aquavan probably would have done the job better, Guilford said in a press release, and officials will be talking with the FDA in the next few weeks about how to proceed.

Jurchison told BioWorld Today that the company considers "between three and six months" a reasonable period during which to decide whether to amend dosing, amend the program or both in order to get the best label - but the FDA, of course, will make the final call.

"We have a lot of data already from the Phase II program, this trial and ongoing Phase III studies," she said. "We'll synthesize those data and have our meeting with the FDA. We need to come back [to the agency] with greater clarity."

Through a $7 million stock deal with Lawrence, Kan.-based ProQuest Pharmaceuticals Inc., Guilford gained full rights late last year to Aquavan, which it had been developing since the spring of 2000. The firms entered a license agreement that year. (See BioWorld Today, Dec. 3, 2004.)

Guilford has two marketed products - Gliadel Wafer, which is polifeprosan 20 with carmustine implant for brain cancer, and Aggrastat (tirofiban hydrochloride), an injectable glycoprotein IIb/IIIa receptor antagonist for acute coronary syndrome.

Aggrastat also is in Phase III trials for percutaneous coronary intervention, and, earlier this month Guilford reported that additional data from its ADVANCE trial showed that a single high-dose bolus regimen improved outcomes in diabetic patients. In 2003, Guilford paid Whitehouse Station, N.J.-based Merck & Co. Inc. $84 million for the rights to the drug. (See BioWorld Today, Oct. 30, 2003.)

Jurchison pointed to the "good diversity" in the pipeline further back, and called Aquavan important.

"We still believe it's a significant product for Guilford," she said.

Also in Phase III, Guilford has Dopascan, an imaging agent to diagnose and monitor Parkinson's disease.